The present invention relates to medications and, more particularly, to a prepackaged syringe or container, such as a vial, containing a predetermined and premeasured concentration of a substance, such as dextrose, anthocyanins, anthocyanidins and/or their metabolites, optionally including one or more bioactive reagents.
Prolotherapy is also known as “proliferation therapy,” “regenerative injection therapy,” or “proliferative injection therapy”. It involves injecting an otherwise non-pharmacological and non-active irritant solution into the body, generally in the region of tendons or ligaments for the purpose of strengthening weakened connective tissue and alleviating musculoskeletal pain.
Prolotherapy was originally hypothesized to reinitiate the inflammatory process that deposits new additional fibers thereby repairing lax tendons or ligaments and to possibly promote the release of local growth factors. Once strengthened, the weak areas would no longer send pain signals.
Subsequently, reports of physiological changes to synovial joints have been reported following dextrose intra-articular injection. (Reeves K D, Hassanein K: Randomized prospective double blind placebo controlled study of dextrose prolotherapy of knee osteoarthritis with and without ACL laxity. Alt Ther Hlth Med 2000;6(2):37-46. Reeves K D, Hassanein K: Randomized prospective double blind placebo controlled study of dextrose prolotherapy of osteoarthritic thumbs and finger (DIP, PIP and trapeziometacarpal joints) Evidence of Clinical Efficacy. Jnl Alt Compl Med 2000;6(4):311-320. Reeves K D, Hassanein K: Long term effects of dextrose prolotherapy for anterior cruciate ligament laxity: A prospective and consecutive patient study. Alt Ther Hlth Med 2003;9(3)58-62.)
These results were without explanation at the time. Referring to FIGS. 3 and 4, subsequent proof of principle studies on human synovial explants by the applicant showed that various levels of dextrose resulted in the human synovium producing insulin stimulating growth hormone (IGF-1) and turning the gene on for same. The low glucose in medium was 1 gram glucose per liter and the higher dose was 4.5 grams of glucose per liter in the culture media.
These observations suggested that the dextrose injection was not just a sclerosing agent as previously proposed, but one that incited the local tissues to produce a growth hormone(s). There is medical literature support for this concept. (Murphy M, Godson C, Cannon S, Kato S, Mackenzie H S, Martin F, Brady H R. Suppression Subtractive Hybridization Identifies High Glucose Levels as a Stimulus for Expression of Connective Tissue Growth Factor and Other Genes in Human Mesangial Cells. J Bio Chem, 274, 5830-5834.) They reported that that the tissue glucose was 0.1% and the injection raised the level to 0.45%. Within 20 minutes of the glucose injection there were fifteen different proteins identified including connective tissue growth factor (CTGF) and transforming growth factor beta (TGF-(β1).
Armed with the in vitro study results, a proof of principle clinical trial was performed on 6 subjects. They all had radiological imaging evidence of exposed bone on medial compartment of the knee joint. They had arthroscopic inspection and video documentation of their lesion. The video records were libraried for subsequent comparison. They were given monthly injections of 9 cc or 12.5% dextrose. Subsequently arthroscopic inspection between 8 and 12 months showed the regrowth of articular cartilage in area previously denuded. Biopsy of these areas showed hyaline cartilage, supported by histochemical characteristics and type II collagen.
Prolotherapy has rapidly expanding indications based upon clinical results. Its use in arthritic joints has been reported. (Murphy M, Godson C, Cannon S, Kato S, Mackenzie H S, Martin F, Brady H R. Suppression Subtractive Hybridization Identifies High Glucose Levels as a Stimulus for Expression of Connective Tissue Growth Factor and Other Genes in Human Mesangial Cells. J Bio Chem, 274, 5830-5834.) (Dumais R, Benoit C, Dumais A, Babin L, Bordage R, deArcos C, Allard J, Belanger. Effect of Regenerative Injection Therapy on Function and Pain in Patients with Knee Osteoarthritis: A Randomized Crossover Study. Pain Medicine 2012 Jul. 3. doi: 10.1111/j.1526-4637.2012.01422.x. [Epub ahead of print]) (Rabado D, Zgierska A, Fortney L, Kijowski R, Mundt M, Ryan M, Grettie J, Patterson J J. Hypertonic dextrose injections (prolotherapy) for knee osteoarthritis: results of a single-arm uncontrolled study with 1-year follow-up. J Altern Complement Med. 2012 April;18(4):408-14.)
Dextrose prolotherapy injections have been used for Osgood Slater's Disease, a non union of bone at the tibial tubercle. (Topol G A, Podesta L A, Reeves K D, Raya F, Fullerton D B, Yeh H. Hyperosmolar Dextrose Injection for Recalcitrant Osgood-Schlatter Disease. Pediatrics. 2011 November;128(5) 121-8.; originally published online Oct. 3, 2011).
Prolotherapy was popularized in the 1950's. (Hackett G S. Ligament and Tendon Relaxation treated by Prolotherapy: 1st edition 1956). It is practiced by thousands of health care providers at this time. The practice includes injections of both intra-articular and various extra articular tissues.
The ancient practice of each practitioner mixing their own concentrations of reagents has not changed since the conception. The commonly used material is dextrose liquid of a percent greater than physiologic. This requires each practitioner to purchase separately the containers or syringes. They must buy the dextrose and the vehicle, such as normal (0.9%) saline, Ringer's lactate solution, or the like. They then must mix at their location. This is labor intensive and inefficient. The practitioner often adds other reagents that would enhance a tissue reaction, but not one that would be known to promote growth hormone production. This conventional method does not insure or validate sterility. Moreover, this conventional method lacks standardization and the concentration of dextrose delivered can vary depending on the accuracy of the person mixing the various components. Finally, the shelf life of the components is not reliable or standardized.
There is currently no commercially available, prepackaged product to facilitate the process, insure sterility and uniform concentrations of dextrose, various anthocyanins, anthocyanidins, their metabolites, and/or bioreactive reagent(s).
As can be seen, there is a need for a prepackaged syringe or container, such as a vial, containing a predetermined and premeasured substance, such as dextrose, anthocyanins, anthocyanidins, or the like, in a desired concentration, optionally including one or more bioactive reagents.